Neural and Cognitive Predictors of Stimulant Treatment Efficacy in Medication-Naïve ADHD Adults: A Pilot Diffusion Tensor Imaging Study.

OBJECTIVE: Stimulant medications are the main treatment for Attention Deficit Hyperactivity Disorder (ADHD), but overall treatment efficacy in adults has less than a 60% response rate. This study aimed to identify neural and cognitive markers predictive of longitudinal improvement in response to stimulant treatment in drug-naïve adults with ADHD. METHOD: We used diffusion tensor imaging (DTI) and executive function measures with 36 drug-naïve adult ADHD patients in a prospective study design. RESULTS: Structural connectivity (measured by fractional anisotropy, FA) in striatal regions correlated with ADHD clinical symptom improvement following stimulant treatment (amphetamine or methylphenidate) in better medication responders. A significant positive correlation was also found between working memory performance and stimulant-related symptom improvement. Higher pre-treatment working memory scores correlated with greater response. CONCLUSION: These findings provide evidence of pre-treatment neural and behavioral markers predictive of longitudinal treatment response to stimulant medications in adults with ADHD.

Distinct and shared white matter abnormalities when ADHD is comorbid with ASD: A preliminary diffusion tensor imaging study.

Attention deficit/hyperactivity disorder (ADHD), a common neurodevelopmental disorder, is the most frequent comorbid condition seen in children with autism spectrum disorder (ASD). This high comorbidity between ADHD and ASD worsens symptom manifestations and complicates disease treatment and prognosis. It remains unclear whether individuals suffering with both ADHD and ASD, compared to individuals with ADHD only, share overlapping neural correlates associated with ADHD neuropathology, or exhibit a distinct neuropathological profile. Answering this question is critical to the understanding of treatment outcomes for the challenging comorbid ADHD symptoms. To identify the shared and the differentiated neural correlates of the comorbidity mechanisms of ADHD with ASD, we use diffusion tensor imaging (DTI) to characterize white-matter microstructure integrity in youth diagnosed with ADHD+ASD and youth with ADHD-only (excluding both the diagnosis and symptoms of ASD) compared with a healthy control group. Results show that the ADHD-only cohort exhibits impaired microstructural integrity (lower fractional anisotropy, FA) in the callosal-cingulum (CC-CG) tracts compared to the control cohort. The ADHD+ASD comorbid cohort shows impaired FA in an overlapping region within the CC-CG tracts and, additionally, shows impaired FA in the frontolimbic tracts including the uncinate fasciculus and anterior thalamic radiation. Across all participants, FA in the CC-CG showed a significantly negative relationship with the degree of ADHD symptom severity. Findings of this study suggest a specific role of CC-CG underlying ADHD neuropathology and symptom manifestations, and when comorbid with ASD a shared ADHD profile with a shift toward an anterior-brain, frontal impact. Results of this study may facilitate future targeted therapeutics and assist in diagnostic precision for individuals suffering with differing levels of comorbid ADHD with ASD, and ultimately contribute to improve prognostication and outcomes for these two highly prevalent and comorbid neurodevelopmental disorders.

Memory retrieval brain-behavior disconnection in mild traumatic brain injury: A magnetoencephalography and diffusion tensor imaging study.

Mild traumatic brain (mTBI) injury is often associated with long-term cognitive and behavioral complications, including an increased risk of memory impairment. Current research challenges include a lack of cross-modal convergence regarding the underlying neural-behavioral mechanisms of mTBI, which hinders therapeutics and outcome management for this frequently under-treated and vulnerable population. We used multi-modality imaging methods including magnetoencephalography (MEG) and diffusion tensor imaging (DTI) to investigate brain-behavior impairment in mTBI related to working memory. A total of 41 participants were recruited, including 23 patients with a first-time mTBI imaged within 3 months of injury (all male, age = 29.9, SD = 6.9), and 18 control participants (all male, age = 27.3, SD = 5.3). Whole-brain statistics revealed spatially concomitant functional-structural disruptions in brain-behavior interactions in working memory in the mTBI group compared with the control group. These disruptions are located in the hippocampal-prefrontal region and, additionally, in the amygdala (measured by MEG neural activation and DTI measures of fractional anisotropy in relation to working memory performance; p < .05, two-way ANCOVA, nonparametric permutations, corrected). Impaired brain-behavior connections found in the hippocampal-prefrontal and amygdala circuits indicate brain dysregulation of memory, which may leave mTBI patients vulnerable to increased environmental demands exerting memory resources, leading to related cognitive and emotional psychopathologies. The findings yield clinical implications and highlight a need for early rehabilitation after mTBI, including attention- and sensory-based behavioral exercises.